Scientists tie 'biological clock' to sudden, fatal heart attacks

PARIS--Scientists on Wednesday said they had uncovered the first molecular proof that the "biological clock" is linked to a type of sudden, fatal heart attack.

Ventricular arrhythmia, or abnormal heartbeat, occurs most frequently after waking in the morning — and also to a lesser degree in the evening hours — and causes a high number of deaths.

Reporting in the journal Nature, researchers in the United States said they had uncovered the first molecular link between this risk and circadian rhythm, the term by which biological processes vary according to a 24-hour period.

The finger points at levels of a protein called Klf15, they said.

Previous research has found Klf15 to be a circadian controller — and, startlingly, is also lacking among some patients with heart failure.

The team created mice that had been genetically engineered to either lack Klf15 or make the protein excessively.

In both cases, the rodents had a much higher risk of arrhythmias compared to normal counterparts.

"It is the first example of a molecular mechanism for the circadian change in susceptibility to cardiac arrhythmias," said Xander Wehrens of Baylor College School of Medicine in Houston, Texas.

"If there was too much Klf15 or none, the mice were at risk for developing the arrhythmia."

Klf15 is only one step in a complex molecular cascade, the researchers believe.

It controls another protein, KChIP2, which affects potassium-generated electrical current that flows though heart muscle cells called cardiac myocytes.

When levels of KChIP2 fluctuate, this causes electrical instability in the myocytes.

As a result, the heart muscle's action becomes impaired and it takes longer (or conversely, less time) to empty the ventricle — the heart's pumping chamber. The heart loses the regularity of the beat and labors to pump blood efficiently.

Co-author Mukesh Jain of the Case Western Reserve University School of Medicine in Cleveland, Ohio said that further work could well uncover other circadian-related causes.

The discovery opens up intriguing paths of research, in pinpointing individuals at risk of nocturnal death and devising drugs to shield them, Jain added.